The program concerns the structure, metabolism and function of protein-acid mucopolysaccharide complexes in normal individuals and patients with connecitve tissue disease. Emphasis continues to be placed on the anabolism and catabolism of the protein-chondroitin sulfate-keratan sulfate complex. Studies on the biosynthesis of the carbohydrate portion of this complex focus on involvement of nucleotide and/or polyisoprenoid phospho di- and oligosaccharides as immediate precursors of growing polysaccharide chains; catabolic studies continue to plase emphasis on purification of mammalian glycosidases and sulfatases required for degradation and involve purification of glycosidases by affinity column chromatography. Recent isolation of an endo Beta-galactosidase acting on keratan sulfate has allowed studies to be initiated to elucidate the nature of the linkage region(s) between keratan sulfate and the polypeptide core. The mechanism of action of a mammalian Beta-galactosidase in the "correction" of accumulation of S35-containing material in generalized gangliosidosis fibroblasts is under study. In related studies the substituents of the protein-chondroitin sulfate-keratan sulfate complex found in normal articular cartilage and those from patients with connective tissue disease continue to be studied to determine 1) whether antigenic alterations of the cartilage matrix or its degradation products occur and 2) whether an autoimmune response may result from prolonged exposure of tissue to "sensitized" cartilage components.